The role of changes in the receptor repertoire diversification process in either lymphocytes and/or accessory cells in causing the latered immunological phenotypes associated with ageing will be investigated. Quantitative antibody responses to a variety of antigens, and development of cytotoxic responses to a panel of MHC haplotypes, will be assessed after polyclonal activation. In addition the heterogeneity of the response to a selected antigen will be analysed by isoelectric focussing (of antibody), or inhibition of binding (or cytotoxicity) using anti-idiotypic antibodies made to antigen-specific cell bound receptors. Potential changes with age in the diversifying elements within the host (e.g., the reticuloendothelial cells in the thymus) will be examined by comparing the MHC restriction imposed in young or old B (T) lymphocytes by differentiation in allogeneic or syngeneic environments. Heterogeneity in the receptor repertoire of antigen recognition (or antigen-presenting) cells in aged animals, and development of those cells in different aged hosts from progenitors of young or aged mice will be investigated by comparing the ability of the antigen-presenting cells to present a variety of antigens in an immunogenic form to a potentially responding pool of (B plus T) lymphocytes. Finally, the possibility that a change occurs in the regulatory interactions of a complex network of antigen specific B and T cells in young/old mice will be studied by comparing the self preference (for interactions of hapten-carrier primed (B plus T) cells to generate secondary antibody responses in vitro) in isolated B and T lymphocytes of individual young or old animals.